Rescue factor VIII replacement to secure hemostasis in a patient with hemophilia A and inhibitors on emicizumab prophylaxis undergoing hip replacement

Management of bleeding and invasive procedures in haemophilia A patients with inhibitor treated with emicizumab (Hemlibra®): Proposals from the French network on inherited bleeding disorders (MHEMO), the French Reference Centre on Haemophilia, in collaboration with the French Working Group on Perioperative Haemostasis (GIHP)

“…If rFVIIa combined with tranexamic acid is inefficient (persistence of bleeding despite three injections at 2 or 3 hours intervals at a dose of 90 µg/kg), and if the anti‐FVIII inhibitor titre is low (<5 BU/mL), infusion of human FVIII concentrate can also be considered within 2‐3 hours after the last rFVIIa administration . This underlines that inhibitor titration, which is not performed in all centres, should be part of the routine follow‐up of patients with inhibitors treated with emicizumab.…”

“…In the case of a severe bleeding, the dose of FVIII required should be calculated on the basis of the inhibitor titre (<5 BU/mL) and in order to maintain FVIII above 80 IU/dL at least during the first 48 hours. To maintain this target, it may be sometimes required to increase the frequency of bolus injections, and even to switch to continuous infusion . Plasma FVIII concentrations should be monitored using a chromogenic assay method using bovine reagents (no interference with the presence of emicizumab).…”

Emicizumab treatment and monitoring in a paediatric cohort: real‐world data

“…11 Guidelines for the management of patients treated by emicizumab who require surgical interventions have not yet been well established. [12][13][14] Emicizumab treatment may be associated with several risks, such as the development of antidrug antibodies, loss of efficacy, thrombosis, and thrombotic microangiopathy (TMA). 5,15 Therefore, ancillary laboratory tests for monitoring the results of therapy may be valuable, but the most beneficial assay of choice remains to be elucidated.…”

Major surgery management in patients with haemophilia A and inhibitors on emicizumab prophylaxis without global coagulation monitoring

“…A few case reports (i.e. two hip replacements and one knee replacement) also have been published with different strategies and outcomes (Kizilocak et al , ; Santagostino et al , ; Seaman & Ragni, ) (Table ). Severe adverse events, including thrombotic microangiopathy (TMA), thrombosis and skin necrosis, were observed when emicizumab was co‐administered with aPCC (but not rFVIIa or FVIII concentrates) at cumulative doses >100 iu/kg/day and for >1 day (Oldeburg et al , ).…”

“…Kizilocak et al ( ) demonstrated the utility of preoperative TGA for tailoring bypassing therapy in a 25‐year‐old man who underwent knee arthroplasty before the recommendation of not using emicizumab with aPCC. Conversely, TGA could not predict the occurrence of bleeding complications in a patient who underwent surgery and was treated with emicizumab and rFVIIa (Santagostino et al , ). Morover, TGA does not reflect the fibrin clot stability, which is essential for complete haemostasis.…”